On Ohta's hypothesis: Most amino acid substitutions are deleterious

Ohta's hypothesis that most amino acid substitutions are deleterious grew out of a class of population-genetics models called shift models. Recently, shift models have been shown to be biologically unreasonable and have been replaced by a more plausible house-of-cards model. In this paper, the simplest form of the house-of-cards models is shown to be incompatible with most of the major features of protein evolution. Moreover, this model is shown to not be a model of exclusively deleterious-allele evolution, but rather to be a model with an equal mix of deleterious and advantageous substitutions.